The Evaluation of Sevoflurane-Induced Apoptotic Neurodegeneration with MicroPET Using [18F]-DFNSH in the Developing Rat Brain
Author(s): Shuliang Liu, Merle G Paule, Xuan Zhang, Glenn D Newport, Scott M Apana, Marc S Berridge, Tucker A Patterson, Syed F Ali, William Slikker Jr, and Cheng Wang
General anesthetic-induced apoptotic neurodegeneration confirmed in animal models caused substantial concerns over the safety of pediatric patients undergoing general anesthesia. Therefore, studies in search of translational molecular probes for labeling apoptotic neurons are imperative. The purpose of the current study is to examine the utility of [18F]-DFNSH as an apoptosis probe for positron emission tomography (PET) in evaluating sevofluraneinduced neuronal apoptosis in the developing rat brain. Neonatal rats were exposed to 2.5% sevoflurane for 3, 6, or 9 h on postnatal day (PND) 7. MicroPET scans using [18F]-DFNSH as radiotracer were performed in weeks 1, 3, or 8 after sevoflurane exposure, respectively. In week 1 or 3 after sevoflurane exposure, standard uptake values (SUVs) in frontal cortex in the 9-h-exposed rats, but not in 3- or 6-h-exposed rats, are significantly higher than those of the controls, suggesting increased uptake and retention of [18F]-DFNSH. Interestingly, the uptake of this tracer was attenuated in 9-h-exposed rats when co-administered with L-carnitine. Collectively, the results suggest that [18F]-DFNSH-PET studies can help define the temporal course of sevoflurane-induced apoptosis in the developing rat brain.